title: Toxic effects of catecholamines on skin.
abstract: The purpose of this study was to examine the effects of catecholamines on skin necrosis independent of their vasoactive effects. Rat abdominal or human breast skin was excised, pinned flat, and incubated at 37 degrees C for 6 hours in a buffered salt solution containing catecholamine. At 0.1 and 6 hours the lactate dehydrogenase (LDH) released from the skin and appearing in the buffer was determined spectrophotometrically. All groups showed similar LDH levels at 0.1 hour. Rat skin treated with greater than or equal to 10(-7) M epinephrine (33 times less than the 1:200,000 used clinically) or greater than or equal to 10(-5) M norepinephrine showed a significant increase in the LDH released at 6 hours versus controls (18.75 +/- 1.25 versus 13.75 +/- 1.25 and 29.25 +/- 2.96 versus 22.00 +/- 1.96 IV, respectively). Total tissue LDH levels were not significantly different at 0.1 or 6 hours. The toxic effect of epinephrine was eliminated by the addition of propranolol or selective beta 2 blockade, but not by alpha or beta 1 blockade. Therefore, this effect appears to be mediated largely by beta 2 receptors. Similar toxic effects were seen in human breast skin treated with 1:200,000 epinephrine and were blocked with propranolol. Phenylephrine at 1:20,000 demonstrated toxicity, but angiotensin II and vasopressin did not. These studies indicate that addition of catecholamine to ischemic rat or human skin accelerates skin death within 6 hours, but that the toxicity can be reversed with beta blockade.
authors.affiliation: Plastic Surgery Research Laboratories, Duke University Medical Center, Durham, N.C.
authors.forename: R W
authors.initials: RW
authors.lastname: Burk
authors.forename: D
authors.initials: D
authors.lastname: Serafin
authors.forename: B
authors.initials: B
authors.lastname: Klitzman
mesh_terms: D000804:Angiotensin II / Q000633:toxicity; D000818:Animals; D004837:Epinephrine / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000633:toxicity*; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000633:toxicity; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000187:drug effects* / Q000201:enzymology; D014662:Vasoconstrictor Agents / Q000633:toxicity; D014667:Vasopressins / Q000633:toxicity
chemical_list: D014662:Vasoconstrictor Agents; D014667:Vasopressins; D000804:Angiotensin II; D010656:Phenylephrine; D011433:Propranolol; D007770:L-Lactate Dehydrogenase; D009638:Norepinephrine; D004837:Epinephrine; D010646:Phentolamine